Neurological recovery in patients with severe spinal cord injury (SCI) is extremely rare. We have identified a patient with chronic cervical traumatic SCI, who suffered a complete loss of motor and ...sensory function below the injury for 6 weeks after the injury, but experienced a progressive neurological recovery that continued for 17 years. The extent of the patient's recovery from the severe trauma-induced paralysis is rare and remarkable. A detailed study of this patient using diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), and resting state fMRI (rs-fMRI) revealed structural and functional changes in the central nervous system that may be associated with the neurological recovery. Sixty-two percent cervical cord white matter atrophy was observed. DTI-derived quantities, more sensitive to axons, demonstrated focal changes, while MTI-derived quantity, more sensitive to myelin, showed a diffuse change. No significant cortical structural changes were observed, while rs-fMRI revealed increased brain functional connectivity between sensorimotor and visual networks. The study provides comprehensive description of the structural and functional changes in the patient using advanced MR imaging technique. This multimodal MR imaging study also shows the potential of rs-fMRI to measure the extent of cortical plasticity.
Background and Aims:
The Crohn’s Disease Endoscopic Index of Severity CDEIS and Simplified Endoscopic Score for Crohn’s Disease SES-CD demonstrate consistent overall intra- and inter-rater ...reliability. However, the reliability of some index items is relatively poor. We evaluated scoring conventions to improve the reliability of these items.
Methods:
Five gastroenterologists with no previous experience scoring the CDEIS or SES-CD were trained on their use. A total of 65 video recordings of colonoscopies were scored blindly by each gastroenterologist before and after additional training on index scoring conventions. Intra-class correlation coefficients ICCs assessed the effect of application of these conventions on the reliability of the CDEIS, SES-CD, and a Global Evaluation of Lesion Severity GELS score.
Results:
Following training on scoring conventions, inter-rater ICCs (95% confidence interval CI) for the total SES-CD score increased from 0.78 0.71, 0.85 to 0.85 0.79, 0.89. The ICCs for the total CDEIS and GELS scores were not affected: corresponding inter-rater ICCs were 0.74 0.65, 0.81 and 0.49, 0.38, 0.61 before and 0.73 0.65, 0.81 and 0.53 0.42, 0.64 following application of scoring conventions. Estimations of ulcer depth, surface area, anatomical location, and stenosis were important sources of variability.
Conclusions:
Use of scoring conventions previously developed by expert central readers enhanced the reliability of the SES-CD but did not similarly affect the CDEIS or GELS. As the SES-CD is more likely to be reliable than the CDEIS and can be optimised with targeted training, it is the preferred instrument for use in clinical trials.
Although corticosteroids are effective for induction of remission of Crohn's disease, many patients relapse when steroids are withdrawn or become steroid dependent. Furthermore, corticosteroids ...exhibit significant adverse effects. The success of methotrexate as a treatment for rheumatoid arthritis led to its evaluation in patients with refractory Crohn's disease. Methotrexate has been studied for induction of remission of refractory Crohn's disease and has become the principal alternative to azathioprine or 6-mercaptopurine therapy. This systematic review is an update of a previously published Cochrane review.
The primary objective was to assess the efficacy and safety of methotrexate for induction of remission in patients with active Crohn's disease in the presence or absence of concomitant steroid therapy.
We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD/FBD group specialized register from inception to June 27, 2012 for relevant studies. Conference proceedings and reference lists were also searched to identify additional studies.
Randomized controlled trials of methotrexate compared to placebo or an active comparator for treatment of active refractory Crohn's disease in adult patients (> 17 years) were considered for inclusion.
The primary outcome was failure to failure to enter remission and withdrawal from steroids. Secondary outcomes included adverse events, withdrawal due to adverse events, serious adverse events and quality of life. We calculated the relative risk (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention to treat basis. The Cochrane risk of bias tool was used to assess the methodological quality of included studies. The GRADE approach was used to assess the overall quality of evidence supporting the primary outcome.
Seven studies (495 patients) were included. Four studies were rated as low risk of bias. Three studies were rated as high risk of bias due to open label or single-blind designs. The seven studies differed with respect to participants, intervention, and outcomes to the extent that it was considered to be inappropriate to pool the data for meta-analysis. Three small studies which employed low doses of oral methotrexate showed no statistically significant difference in failure to induce remission between methotrexate and placebo or between methotrexate and 6-mercaptopurine. For the study using 15 mg/week of oral methotrexate 33% (5/15) of methotrexate patients failed to enter remission compared to 11% (2/18) of placebo patients (RR 3.00, 95% CI 0.68 to 13.31). For the study using 12.5 mg/week of oral methotrexate 81% (21/26) of methotrexate patients failed to enter remission compared to 77% (20/26) of placebo patients (RR 1.05, 95% CI 0.79 to 1.39). This study also had an active comparator arm, 81% (21/26) of methotrexate patients failed to enter remission compared to 59% (19/32) of 6-mercaptopurine patients (RR 1.36, 95% CI 0.97 to 1.92). For the active comparator study using 15 mg/week oral methotrexate, 20% (3/15) of methotrexate patients failed to enter remission compared to 6% of 6-mercaptopurine patients (RR 3.20, 95% CI 0.37 to 27.49). This study also had a 5-ASA arm and found that methotrexate patients were significantly more likely to enter remission than 5-ASA patients. Twenty per cent (3/15) of methotrexate patients failed to enter remission compared to 86% (6/7) of 5-ASA patients (RR 0.23, 95% CI 0.08 to 0.67). One small study which used a higher dose of intravenous or oral methotrexate (25 mg/week) showed no statistically significant difference between methotrexate and azathioprine. Forty-four per cent (12/27) of methotrexate patients failed to enter remission compared to 37% of azathioprine patients (RR 1.20, 95% CI 0.63 to 2.29). Two studies found no statistically significant difference in failure to enter remission between the combination of infliximab and methotrexate and infliximab monotherapy. One small study utilized intravenous methotrexate (20 mg/week) for 5 weeks and then switched to oral (20 mg/week). Forty-five per cent (5/11) of patients in the combination group failed to enter remission compared to 62% of infliximab patients (RR 0.73, 95% CI 0.31 to 1.69) The other study assessing combination therapy utilized subcutaneous methotrexate (maximum dose 25 mg/week). Twenty-four per cent (15/63) of patients in the combination group failed to enter remission compared to 22% (14/63) of infliximab patients (RR 1.07, 95% CI 0.57 to 2.03). A large placebo-controlled study which employed a high dose of methotrexate intramuscularly showed a statistically significant benefit relative to placebo. Sixty-one per cent of methotrexate patients failed to enter remission compared to 81% of placebo patients (RR 0.75, 95% CI 0.61 to 0.93; number needed to treat, NNT=5). Withdrawals due to adverse events were significantly more common in methotrexate patients than placebo in this study. Seventeen per cent of methotrexate patients withdrew due to adverse events compared to 2% of placebo patients (RR 8.00, 95% CI 1.09 to 58.51). The incidence of adverse events was significantly more common in methotrexate patients (63%, 17/27) than azathioprine patients (26%, 7/27) in one small study (RR 2.42, 95% CI 1.21 to 4.89). No other statistically significant differences in adverse events, withdrawals due to adverse events or serious adverse events were reported in any of the other placebo-controlled or active comparator studies. Common adverse events included nausea and vomiting, abdominal pain, diarrhea, skin rash and headache.
There is evidence from a single large randomized trial which suggests that intramuscular methotrexate (25 mg/week) provides a benefit for induction of remission and complete withdrawal from steroids in patients with refractory Crohn's disease. Lower dose oral methotrexate does not appear to provide any significant benefit relative to placebo or active comparator. However, these trials were small and further studies of oral methotrexate may be justified. Comparative studies of methotrexate to drugs such as azathioprine or 6-mercaptopurine would require the randomization of large numbers of patients. The addition of methotrexate to infliximab therapy does not appear to provide any additional benefit over infiximab monotherapy. However these studies were relatively small and further research is needed to determine the role of methotrexate when used in conjunction with infliximab or other biological therapies.
To describe the prevalence of osteoporosis and its association with functional electrical stimulation (FES) use in individuals with spinal cord injury (SCI)-related paralysis.
Retrospective ...cross-sectional evaluation.
Clinic.
Consecutive persons with SCI (N=364; 115 women, 249 men) aged between 18 and 80 years who underwent dual-energy x-ray absorptiometry (DXA) examinations.
Not applicable.
Prevalence of osteoporosis defined as DXA T score ≤-2.5.
The prevalence of osteoporosis was 34.9% (n=127). Use of FES was associated with 31.2% prevalence of osteoporosis compared with 39.5% among persons not using FES. In multivariate adjusted logistic regression analysis, FES use was associated with 42% decreased odds of osteoporosis after adjusting for sex, age, body mass index, type and duration of injury, Lower Extremity Motor Scores, ambulation, previous bone fractures, and use of calcium, vitamin D, and anticonvulsant; (adjusted odds ratio OR=.58; 95% confidence interval CI, .35-.99; P=.039). Duration of injury >1 year was associated with a 3-fold increase in odds of osteoporosis compared with individuals with injury <1 year; (adjusted OR=3.02; 95% CI, 1.60-5.68; P=.001).
FES cycling ergometry may be associated with a decreased loss of bone mass after paralysis. Further prospective examination of the role of FES in preserving bone mass will improve our understanding of this association.
Background In most studies, home dialysis associates with greater survival than facility hemodialysis (HD). However, the relationship between mortality risk and modality can vary by era. We describe ...and compare changes in survival with facility HD, peritoneal dialysis, and home HD over a 15-year period using data from The Australia and New Zealand Dialysis and Transplant Registry (ANZDATA). Study Design An observational inception cohort study, using Cox proportional hazards and competing-risks regression. Setting & Participants All adult patients initiating renal replacement therapy in Australia and New Zealand since March 31, 1998, followed up to December 31, 2012. Predictor Era at dialysis inception (1998-2002, 2003-2007, and 2008-2012). We adjusted for time-varying dialysis modality and comorbid conditions, demographics, initial state/country of treatment, late referral for nephrology care, primary kidney disease, and kidney function at dialysis inception. Outcomes Patient mortality. Results Survival on dialysis therapy has improved despite increasing patient comorbid conditions. Compared to 1998 to 2002, there has been a 21% reduction in mortality for those on facility HD therapy, a 27% reduction for those on peritoneal dialysis therapy, and a 49% reduction for those on home HD therapy. Limitations Potential for residual confounding from limited collection of comorbid conditions; analyses lack data for blood pressure, fluid volume status, socioeconomics, medication, and biochemical parameters. Conclusions Our study indicates that outcomes on dialysis therapy are improving with time and that this improvement is most marked with home dialysis modalities, especially home HD. This might be the result of better dialysis care (eg, improving predialysis care and more appropriate selection of patients for home dialysis). Other contributing factors are possible, such as improvements in general care of patient comorbid conditions and improvements in dialysis technology, although further research is needed to clarify these issues.
Severe asthma leads to debilitating symptoms for patients and excessive socioeconomic burden for the community. Comprehensive models of care are required to address complex issues, risk factors and ...comorbidities in patients with severe asthma, and to identify patients most appropriate for specialised treatments. Dedicated severe asthma services improve asthma control, reduce asthma exacerbations and hospital admissions, and improve quality of life. Currently, diverse models of care exist for managing severe asthma across Australia. Most referrals to severe asthma services are from respiratory physicians seeking a second opinion or from primary care for poorly controlled asthma. Despite benefits of specialised severe asthma services, many patients are not referred and resources are limited, often resulting in long waiting times. Patient referral is often unstructured and there are considerable variations in the management of severe asthma with limited access to other health care professionals such as speech pathologists and dieticians, and restricted scope to optimise patient work‐up before referral. Ongoing communication between the specialist and referring clinician is essential for continuity of care but is often lacking. Referral pathways can be optimised by developing referral criteria and guidelines to triage patients with severe asthma and to improve resource efficiency. Additional education and tools for assessing and managing severe asthma are needed, and mechanisms should be developed for involving primary care in the management of stabilised patients. Strategies to increase patient access to multidisciplinary services are recommended.
Clinicians are increasingly recognizing severe asthma patients in whom biologics and other add-on therapies lead to dramatic improvement. Currently, there is no agreed-upon super-responder (SR) ...definition.
To survey severe asthma experts using a modified Delphi process, to develop an international consensus-based definition of a severe asthma SR.
The Delphi panel was composed of 81 participants (94% specialist pulmonologists or allergists) from 24 countries and consisted of three iterative online voting rounds. Consensus on individual items, whether acceptance or rejection, required at least 70% agreement by panel members.
Consensus was achieved that the SR definition should be based on improvement across three or more domains assessed over 12 months. Major SR criteria included exacerbation elimination, a large improvement in asthma control (two or more times the minimal clinically important difference), and cessation of maintenance of oral steroids (or weaning to adrenal insufficiency). Minor SR criteria were composed of a 75% exacerbation reduction, having well-controlled asthma, and 500 mL or greater improvement in FEV
. The SR definition requires improvement in at least two major criteria. In the future, the SR definition should be expanded to incorporate quality of life measures, although current tools can be difficult to implement in a clinical setting and further research is needed.
This international consensus-based definition of severe asthma SRs is an important prerequisite for better understanding SR prevalence, predictive factors, and the mechanisms involved. Further research is needed to understand the patient's perspective and to measure quality of life more precisely in SRs.
An aerobic, thermophilic and cellulolytic bacterium, designated strain WKT50.2T, was isolated from geothermal soil at Waikite, New Zealand. Strain WKT50.2T grew at 53-76 °C and at pH 5.9-8.2. The DNA ...G+C content was 58.4 mol%. The major fatty acids were 12-methyl C18 : 0 and C18 : 0. Polar lipids were all linked to long-chain 1,2-diols, and comprised 2-acylalkyldiol-1-O-phosphoinositol (diolPI), 2-acylalkyldiol-1-O-phosphoacylmannoside (diolP-acylMan), 2-acylalkyldiol-1-O-phosphoinositol acylmannoside (diolPI-acylMan) and 2-acylalkyldiol-1-O-phosphoinositol mannoside (diolPI-Man). Strain WKT50.2T utilized a range of cellulosic substrates, alcohols and organic acids for growth, but was unable to utilize monosaccharides. Robust growth of WKT50.2T was observed on protein derivatives. WKT50.2T was sensitive to ampicillin, chloramphenicol, kanamycin, neomycin, polymyxin B, streptomycin and vancomycin. Metronidazole, lasalocid A and trimethoprim stimulated growth. Phylogenetic analysis of 16S rRNA gene sequences showed that WKT50.2T belonged to the class Thermomicrobia within the phylum Chloroflexi, and was most closely related to Thermorudis peleae KI4T (99.6% similarity). DNA-DNA hybridization between WKT50.2T and Thermorudis peleae DSM 27169T was 18.0%. Physiological and biochemical tests confirmed the phenotypic and genotypic differentiation of strain WKT50.2T from Thermorudis peleae KI4T and other members of the Thermomicrobia. On the basis of its phylogenetic position and phenotypic characteristics, we propose that strain WKT50.2T represents a novel species, for which the name Thermorudis pharmacophila sp. nov. is proposed, with the type strain WKT50.2T ( = DSM 26011T = ICMP 20042T). Emended descriptions of Thermomicrobium roseum, Thermomicrobium carboxidum, Thermorudis peleae and Sphaerobacter thermophilus are also proposed, and include the description of a novel respiratory quinone, MK-8 2,3-epoxide (23%), in Thermomicrobium roseum.
Participation in sailing by people with disabilities, particularly in small sailboats, is widely regarded as having positive outcomes on self-esteem and general health for the participants. However, ...a major hurdle for people with no previous experience of sailing, even by those without disabilities, is the perception that sailing is elitist, expensive, and dangerous. Real-time "ride-on" sailing simulators have the potential to bridge the gap between dry-land and on-the-water sailing. These provide a realistic, safe, and easily supervised medium in which nonsailors can easily and systematically learn the required skills before venturing out on the water. The authors report a 12-wk pilot therapeutic sailing program using the VSail-Access sailing simulation system followed by on-water experience. After completion of the training, all subjects demonstrated the ability to navigate a simple course around marker buoys (triangular configuration) on the computer screen, the ability to sail independently in winds of moderate strength (up to 14 knots) on water, and measurable improvements in their psychologic health. In addition, the subjects were able to participate in a sports activity with their respective family members and experienced a sense of optimism about their future.
Chronic neuropathic pain is a common and debilitating consequence of spinal cord injury (SCI). In a rat contusion injury model, we observed that chronic neuropathic pain is present on day 7 after SCI ...and persists for the entire 56-day observation period. However, currently available pain therapies are inadequate for SCI-induced neuropathic pain. In this study, we show that spinal transplantation of mouse embryonic stem cell-derived oligodendrocyte progenitor cells (OPCs) enhances remyelination in the injured spinal cord and reduces SCI-induced chronic neuropathic pain. Moreover, we found that SCI reduces the protein level of neuregulin-1 and ErbB4 in the injured spinal cord and that OPC transplantation enhances the spinal expression of both proteins after SCI. Finally, intrathecal injection of neuregulin-1 small interfering RNA, but not the control nontarget RNA, diminishes OPC transplantation-produced remyelination and reverses the antinociceptive effect of OPC transplantation. Our findings suggest that the transplantation of embryonic stem cell-derived OPCs is an appropriate therapeutic intervention for treatment of SCI-induced chronic neuropathic pain, and that neuregulin-1/ErbB signaling plays an important role in central remyelination under pathological conditions and contributes to the alleviation of such pain.
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